Several metabolic and morphologic changes have been claimed to precede the onset of diabetes, including changes in the pattern and quantity of insulin secretion and alteration in the thickness of capillary basement membranes. Some l0 years ago, Pima Indians with two diabetic parents, and with neither parent diabetic received oral and intravenous glucose tolerance tests, and a biopsy of the quadriceps muscle from which quantitative determinations of the thickness of the capillary basement membrane were made. The same subjects are now being reexamined to determine if their insulin secretion or the thickness of their capillary basement membrane predicted the subsequent development of diabetes, and to determine if there was differential thickening of the muscle capillary basement membrane with increasing age in those with diabetic parents compared to those without. The results will help to determine if vascular lesions at the level of the capillary are present before hyperglycemia develops.